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Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment
Authors:Thaís Helena Gasparoto  Tatiana Salles de Souza Malaspina  Luciana Benevides  Edgard Jose Franco de Melo Jr  Maria Renata Sales Nogueira Costa  José Humberto Damante  Maura Rosane Valério Ikoma  Gustavo Pompermaier Garlet  Karen Angélica Cavassani  João Santana da Silva  Ana Paula Campanelli
Institution:1. Department of Biological Sciences, Bauru Dental School, University of S?o Paulo, Al. Octávio Pinheiro Brisolla, 9-75, CEP 17012-901, Bauru, SP, Brazil
6. Department of Biochemistry and Immunology, School of Medicine of Ribeir?o Preto, University of S?o Paulo, Ribeirao Preto, SP, Brazil
3. Lauro de Souza Lima Institute, Bauru, SP, Brazil
2. Department of Stomatology, Bauru Dental School, University of S?o Paulo, Bauru, SP, Brazil
4. Amaral Carvalho Hospital, Jaú, SP, Brazil
5. Departament of Pathology, Medical School, University of Michigan, Ann Arbor, MI, USA
Abstract:Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that >80% of CD4+CD25+ T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4+CD25+ T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-γ production when compared with CD4+CD25+ T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4+CD25? T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-γ and induced IL-10 and TGF-β secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.
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